U.S. patent number 7,914,808 [Application Number 10/195,341] was granted by the patent office on 2011-03-29 for hybrid biologic/synthetic porous extracellular matrix scaffolds.
This patent grant is currently assigned to DePuy Products, Inc.. Invention is credited to Iksoo Chun, Prasanna Malaviya, Mora C. Melican, Alireza Rezania.
United States Patent |
7,914,808 |
Malaviya , et al. |
March 29, 2011 |
Hybrid biologic/synthetic porous extracellular matrix scaffolds
Abstract
Methods of making a hybrid biologic/synthetic scaffold for
repairing damaged or diseased tissue are provided. The methods
include the step of suspending pieces of an extracellular matrix
material in a liquid to form a slurry, and coating a synthetic mat
with the slurry, or mixing or layering the slurry with a synthetic
polymer solution. The liquid is subsequently driven off so as to
form a foam. Porous implantable scaffolds fabricated by such a
method are also disclosed.
Inventors: |
Malaviya; Prasanna (Ft. Wayne,
IN), Melican; Mora C. (Bridgewater, NJ), Rezania;
Alireza (Hillsborough, NJ), Chun; Iksoo (Flemmington,
NJ) |
Assignee: |
DePuy Products, Inc. (Warsaw,
IN)
|
Family
ID: |
26974784 |
Appl.
No.: |
10/195,341 |
Filed: |
July 15, 2002 |
Prior Publication Data
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Document
Identifier |
Publication Date |
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US 20030021827 A1 |
Jan 30, 2003 |
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Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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60388711 |
Jun 14, 2002 |
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60305786 |
Jul 16, 2001 |
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Current U.S.
Class: |
424/423;
424/422 |
Current CPC
Class: |
A61F
2/30749 (20130101); A61L 31/005 (20130101); A61B
17/064 (20130101); A61L 27/3683 (20130101); A61F
2/3872 (20130101); A61B 17/0642 (20130101); A61L
27/56 (20130101); A61L 27/3629 (20130101); A61L
27/18 (20130101); A61F 2/28 (20130101); A61L
27/3633 (20130101); A61F 2/30756 (20130101); A61L
27/3691 (20130101); A61L 27/18 (20130101); C08L
67/04 (20130101); A61F 2230/0067 (20130101); A61F
2230/0082 (20130101); A61F 2/08 (20130101); A61F
2002/30131 (20130101); A61F 2002/30225 (20130101); A61F
2002/30604 (20130101); A61F 2230/0069 (20130101); A61F
2230/0086 (20130101); A61F 2240/001 (20130101); A61F
2002/2817 (20130101); A61F 2002/30677 (20130101); A61L
2430/06 (20130101); A61B 17/0401 (20130101); A61F
2002/30845 (20130101); A61F 2002/30785 (20130101); A61F
2002/30032 (20130101); A61F 2002/30878 (20130101); A61F
2002/30891 (20130101); A61F 2250/0063 (20130101); A61F
2002/2839 (20130101); A61F 2002/30199 (20130101); A61F
2250/0067 (20130101); A61F 2002/30766 (20130101); A61F
2310/00365 (20130101); A61B 17/06166 (20130101); A61F
2002/30233 (20130101); A61F 2002/30841 (20130101); A61F
2002/30764 (20130101); A61F 2002/30914 (20130101); A61F
2002/30975 (20130101); A61F 2002/30429 (20130101); A61F
2/0811 (20130101); A61F 2220/0025 (20130101); A61F
2240/004 (20130101); A61F 2250/003 (20130101); A61B
2017/00004 (20130101); A61F 2002/30971 (20130101); A61F
2002/30281 (20130101); A61B 2017/0646 (20130101); A61F
2/30965 (20130101); A61F 2002/30293 (20130101); A61F
2002/30957 (20130101); A61F 2230/0013 (20130101); A61B
2017/0475 (20130101); A61F 2230/0091 (20130101); A61F
2/442 (20130101); A61F 2/3094 (20130101); A61F
2002/30224 (20130101); A61F 2002/30261 (20130101); A61F
2002/30217 (20130101); A61F 2002/30892 (20130101); A61F
2002/30294 (20130101); A61F 2002/3096 (20130101); A61F
2002/30751 (20130101); A61F 2002/30153 (20130101); A61B
2017/06057 (20130101); A61F 2002/3021 (20130101); A61F
2230/0063 (20130101); A61F 2/0063 (20130101); A61F
2002/30062 (20130101); A61F 2210/0004 (20130101); A61F
2230/0019 (20130101) |
Current International
Class: |
A61F
2/00 (20060101) |
Field of
Search: |
;424/423,426
;623/11.11 |
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|
Primary Examiner: Barnhart; Lora E.
Attorney, Agent or Firm: Barnes & Thornburg LLP
Parent Case Text
This application claims priority to U.S. Patent Application No.
60/388,711, filed Jun. 14, 2002, and U.S. Provisional Application
No. 60/305,786, filed Jul. 16, 2001, hereby incorporated by
reference.
Cross reference is made to copending U.S. patent application Ser.
No. 10/195,795 entitled "Meniscus Regeneration Device and Method",
DEP-745); Ser. No. 10/195,719 entitled "Devices from Naturally
Occurring Biologically Derived Materials"; Ser. No. 10/195,347
entitled "Cartilage Repair Apparatus and Method"; Ser. No.
10/195,344 entitled "Unitary Surgical Device and Method"; Ser. No.
10/195,606 entitled "Cartilage Repair and Regeneration Device and
Method"; Ser. No. 10/195,354 entitled "Porous Extracellular Matrix
Scaffold and Method"; Ser. No. 10/195,334 entitled "Cartilage
Repair and Regeneration Scaffolds and Method"; and Ser. No.
10/195,633 entitled "Porous Delivery Scaffold and Method", each of
which is assigned to the same assignee as the present application,
each of which is filed concurrently herewith, and each of which is
hereby incorporated by reference. Cross reference is also made to
U.S. patent application Ser. No. 10/172,347 entitled "Hybrid
Biologic-Synthetic Bioabsorbable Scaffolds" which was filed on Jun.
14, 2002, which is assigned to the same assignee as the present
application, and which is hereby incorporated by reference.
Claims
The invention claimed is:
1. A method of making an implantable scaffold for repairing or
regenerating body tissue, the method comprising the steps of:
cutting a naturally occurring extracellular matrix in the presence
of a liquid to produce a cohesive mass of intertwined strips,
ribbons, or fibers; contacting a synthetic polymer with the
cohesive mass to make a composition comprising the cohesive mass
and the polymer; freezing the composition comprising the cohesive
mass and the polymer to form a frozen composition, said frozen
composition comprising crystals, and driving off the crystals to
form a foam.
2. The method of claim 1, further comprising the step of
centrifuging the cohesive mass to compact the cohesive mass prior
to the step of contacting the synthetic polymer with the cohesive
mass.
3. The method of claim 1, wherein the naturally occurring
extracellular matrix is selected from the group consisting of small
intestinal submucosa, stomach submucosa, bladder submucosa,
alimentary submucosa, respiratory submucosa, genital submucosa, and
liver basement membrane.
4. The method of claim 1, wherein the synthetic polymer is formed
as a mat, and said contacting step comprises coating the mat with
the cohesive mass to form a coated mat, prior to the freezing
step.
5. The method of claim 4, wherein the coating step comprises
immersing the mat in the cohesive mass.
6. The method of claim 4, wherein the coating step includes placing
the cohesive mass onto the mat and centrifuging the mat.
7. The method of claim 4, further comprising the step of driving a
needle into the coated mat.
8. A method of making an implantable scaffold comprising the steps
of: comminuting a naturally occurring extracellular matrix in a
liquid to form ribbon-like pieces of the naturally-occurring
extracellular matrix suspended in the liquid and intertwining said
ribbon-like pieces of the naturally-occurring extracellular matrix
by mixing to form a cohesive naturally occurring extracellular
matrix; contacting the cohesive naturally occurring extracellular
matrix with synthetic polymers to form a composition comprising a
cohesive naturally occurring extracellular matrix layer, a
synthetic polymer layer and a transition zone comprising both the
cohesive naturally occurring extracellular matrix and synthetic
polymers; freezing the composition to form a frozen composition,
said frozen composition comprising crystals, and driving off the
crystals to form a foam.
9. A method of making an implantable scaffold comprising the steps
of: cutting a naturally occurring extracellular matrix in the
presence of a liquid to produce a cohesive mass of intertwined
strips, ribbons, or fibers; coating a synthetic polymer mat with
the cohesive mass; freezing the coated mat to form a frozen
composition, said frozen composition comprising crystals, and
driving off the crystals to form a foam coated mat.
10. The method of claim 9, further comprising the steps of: mixing
a composition comprising synthetic polymers with the cohesive mass;
and coating the synthetic mat with the mixture.
11. The method of claim 8, wherein the naturally occurring
extracellular matrix is selected from the group consisting of small
intestine submucosa, stomach submucosa, bladder submucosa,
alimentary submucosa, respiratory submucosa, genital submucosa, and
liver basement membrane.
12. The method of claim 9, wherein the naturally occurring
extracellular matrix is selected from the group consisting of small
intestine submucosa, stomach submucosa, bladder submucosa,
alimentary submucosa, respiratory submucosa, genital submucosa, and
liver basement membrane.
13. The method of claim 8, further comprising the step of allowing
the cohesive naturally occurring extracellular matrix layer and the
synthetic polymer layer to expand and mix with each other for a
length of time prior to the freezing step to increase the width of
the transition zone.
14. The method of claim 1, further comprising the step of
crosslinking the components of the foam.
15. The method of claim 1, wherein the driving off step is
performed by lyophilization of the frozen composition comprising
the cohesive mass and the polymer.
16. The method of claim 1, further comprising the step of adding an
exogenous biologically active agent.
17. The method of claim 16, wherein the biologically active agent
is added prior to the freezing step.
18. The method of claim 16, wherein the biologically active agent
is added after the step of driving off the crystals.
19. The method of claim 1, further comprising the step of shaping
the foam.
20. The method of claim 1 wherein the naturally occurring
extracellular matrix comprises small intestine submucosa.
21. The method of claim 20 wherein the strips, ribbons, or fibers
are about 200 microns thick and 1-5 mm long.
22. The method of claim 8 further comprising the step of
centrifuging the cohesive naturally occurring extracellular matrix,
removing the supernatant, and contacting the resulting compacted,
cohesive naturally occurring extracellular matrix with the
synthetic polymer-comprising composition.
23. The method of claim 9 further comprising the step of
centrifuging the cohesive mass, removing the supernatant, and
mixing the resulting compacted, cohesive mass with the synthetic
polymer mat.
24. The method of claim 8, further comprising the step of
crosslinking the components of the foam.
25. The method of claim 9, further comprising the step of
crosslinking the components of the foam.
26. The method of claim 8, wherein the driving off step is
performed by lyophilization of the frozen composition.
27. The method of claim 8, further comprising the step of adding an
exogenous biologically active agent.
28. A method of making an implantable scaffold for repairing or
regenerating body tissue, the method comprising the steps of: i)
obtaining small intestine submucosa from an animal; ii) placing
said small intestine submucosa into water; iii) cutting said small
intestine submucosa into strips or fibers, wherein said strips or
fibers intertwine; iv) contacting a synthetic polymer with said
intertwined strips of small intestine submucosa to produce a
composition comprising said synthetic polymer and said intertwined
strips of small intestine submucosa; and v) freeze-drying said
composition to yield an implantable scaffold.
Description
TECHNICAL FIELD OF THE DISCLOSURE
The present disclosure relates generally to an extracellular
matrix, scaffold, and more particularly to a porous extracellular
matrix scaffold for repairing or regenerating body tissue and a
method for making such a scaffold.
BACKGROUND AND SUMMARY
Naturally occurring extracellular matrices (ECMs) are used for
tissue repair and regeneration. One such ECM is small intestine
submucosa (SIS). SIS has been used to repair, support, and
stabilize a wide variety of anatomical defects and traumatic
injuries. Commercially-available SIS material is derived from
porcine small intestinal submucosa that remodels the qualities of
its host when implanted in human soft tissues. Further, it is
taught that the SIS material provides a natural matrix with a
three-dimensional microstructure and biochemical composition that
facilitates host cell proliferation and supports tissue remodeling.
SIS products, such as Oasis material and Surgisis material, are
commercially available from Cook Biotech, Bloomington, Ind.
An SIS product referred to as RESTORE.TM. Orthobiologic Implant is
available from DePuy Orthopaedics, Inc. in Warsaw, Ind. The DePuy
product is described for use during rotator cuff surgery, and is
provided as a resorbable framework that allows the rotator cuff
tendon to regenerate itself. The RESTORE.TM. Implant is derived
from porcine small intestine submucosa that has been cleaned,
disinfected, and sterilized. Small intestine submucosa (SIS) has
been described as a naturally-occurring ECM composed primarily of
collagenous proteins. Other biological molecules, such as growth
factors, glycosaminoglycans, etc., have also been identified in
SIS. See Hodde et al., Tissue Eng. 2(3): 209-217 (1996);
Voytik-Harbin et al., J. Cell Biochem., 67:478-491 (1997);
McPherson and Badylak, Tissue Eng., 4(1): 75-83 (1998); Hodde et
al., Endothelium, 8(1):11-24 (2001); Hodde and Hiles, Wounds,
13(5): 195-201 (2001); Hurst and Bonner, J. Biomater. Sci. Polym.
Ed., 12(11) 1267-1279 (2001); Hodde et al., Biomaterial, 23(8):
1841-1848 (2002); and Hodde, Tissue Eng., 8(2): 295-308 (2002), all
of which are incorporated by reference herein. During seven years
of preclinical testing in animals, there were no incidences of
infection transmission form the implant to the host, and the
RESTORE.TM. Implant has not decreased the systemic activity of the
immune system. See Allman et al., Transplant, 17(11): 1631-1640
(2001); Allman et al., Tissue Eng., 8(1): 53-62 (2002).
While small intestine submucosa is available, other sources of
submucosa are known to be effective for tissue remodeling. These
sources include, but are not limited to, stomach, bladder,
alimentary, respiratory, or genital submucosa, or liver basement
membrane. See, e.g., U.S. Pat. Nos. 6,379,710, 6,171,344,
6,099,567, and 5,554,389, hereby incorporated by reference.
Further, while SIS is most often porcine derived, it is known that
these various submucosa materials may be derived from non-porcine
sources, including bovine and ovine sources. Additionally, the ECM
material may also include partial layers of laminar muscularis
mucosa, muscularis mucosa, lamina propria, stratum compactum and/or
other tissue materials depending upon factors such as the source
from which the ECM material was derived and the delamination
procedure.
For the purposes of this invention, it is within the definition of
a naturally occurring ECM to clean, delaminate, and/or comminute
the ECM, or even to cross-link the collagen fibers within the ECM.
It is also within the definition of naturally occurring ECM to
fully or partially remove one or more sub-components of the
naturally occurring ECM. However, it is not within the definition
of a naturally occurring ECM to separate and purify the natural
collagen or other components or sub-components of the ECM and
reform a matrix material from the purified natural collagen or
other components or sub-components of the ECM. While reference is
made to SIS, it is understood that other naturally occurring ECMs
(e.g., stomach, bladder, alimentary, respiratory, and genital
submucosa, and liver basement membrane), whatever the source (e.g.,
bovine, porcine, ovine) are within the scope of this disclosure.
Thus, in this application, the terms "naturally occurring
extracellular matrix" or "naturally occurring ECM" are intended to
refer to extracellular matrix material that has been cleaned,
disinfected, sterilized, and optionally cross-linked. The terms
"naturally occurring extracellular matrix" and "naturally occurring
ECM" are also intended to include ECM foam material prepared as
described in copending U.S. patent application Ser. No. 10/195,354
entitled "Porous Extracellular Matrix Scaffold and Method", filed
concurrently herewith.
The following patents, hereby incorporated by reference, disclose
the use of ECMs for the regeneration and repair of various tissues:
U.S. Pat. Nos. 6,187,039; 6,176,880; 6,126,686; 6,099,567;
6,096,347; 5,997,575; 5,968,096; 5,955,110; 5,922,028; 5,885,619;
5,788,625; 5,762,966; 5,755,791; 5,753,267; 5,711,969; 5,645,860;
5,641,518; 5,554,389; 5,516,533; 5,445,833; 5,372,821; 5,352,463;
5,281,422; and 5,275,826.
The manipulation of scaffold pore size, porosity, and
interconnectivity is of emerging importance in the field of tissue
engineering (Ma and Zhang, 2001, J. Biomed Mater Res. 56(4):
469-477; Ma and Choi, 2001, Tissue Eng., 7(1):23-33), because it is
believed that the consideration of scaffold pore size and
density/porosity influences the behavior of cells and the quality
of tissue regenerated. In fact, several researchers have shown that
different pore sizes influence the behavior of cells in porous
three-dimensional matrices. For example, it has been demonstrated
in the art that for adequate bone regeneration to occur scaffold
pore size should to be at least 100 microns (Klawitter et al.,
1976, J Biomed Mater Res, 10(2):311-323). For pore sizes and
interconnectivity less than that, poor quality bone is regenerated,
and if pore size is between 10-40 microns bone cells are able to
form only soft fibro-vascular tissue (White and Shors, 1991, Dent
Clin North Am, 30:49-67). The current consensus of research for
bone regeneration indicates that the requisite pore size for bone
regeneration is 100-600 microns (Shors, 1999, Orthop Clin North Am,
30(4):599-613; Wang, 1990, Nippon Seikeigeka Gakki Zasshi,
64(9):847-859). It is generally accepted that optimal bone
regeneration occurs for pore sizes between 300-600 microns.
Similarly, for the regeneration of soft orthopaedic tissues, such
as ligament, tendon, cartilage, and fibro-cartilage, scaffold pore
size is believed to have a substantial effect. For example, basic
research has shown that cartilage cells (chondrocytes) exhibit
appropriate protein expression (type II collagen) in scaffolds with
pore sizes of the order of 20 microns and tend to dedifferentiate
to produce type I collagen in scaffolds with nominal porosity of
about 80 microns (Nehrer et al., 1997, Biomaterials,
18(11):769-776). More recently, it has been shown that cells that
form ligaments, tendons, and blood vessels (fibroblasts and
endothelial cells) exhibit significantly different activity when
cultured on scaffolds with differing pore sizes ranging from 5 to
90 microns (Salem et al., 2002, J Biomed Mater Res,
61(2):212-217).
Copending U.S. application Ser. No. 10/195,354 entitled "Porous
Extracellular Matrix Scaffold and Method", DEP-747), filed
contemporaneously herewith and hereby incorporated by reference,
describes methods for making ECM foams wherein the porosity is
controlled. Using the methods so described, ECM foams are made
having the desired porosity for a particular application.
In some applications, it is also desirable to control the rate of
resorption of the scaffold. It is known in the art to make
implantable three-dimensional synthetic scaffolds with controlled
porosity and controlled resorption rates. See, e.g., U.S. Pat. Nos.
6,333,029 and 6,355,699, hereby incorporated by reference. These
synthetic foams may be isotropic in form, or may be anisotropic,
providing various gradient architectures.
In addition to synthetic foams, it is known that resorption rates
of an implant may be controlled by providing a synthetic portion
comprising a perforated or non-perforated sheet or a mat with a
woven, knitted, warped knitted (i.e., lace-like), nonwoven, or
braided structure. It is understood that in any of the above
structures, mechanical properties of the material can be altered by
changing the density or texture of the material. The fibers used to
make the reinforcing component can be for example, monofilaments,
yarns, threads, braids, or bundles of fibers. These fibers can be
made of any biocompatible material. In an exemplary embodiment, the
fibers that comprise the nonwoven or three-dimensional mesh are
formed of a polylactic acid (PLA) and polyglycolic acid (PGA)
copolymer at a 95:5 mole ratio. Illustrated examples of the
synthetic portion also include 90/10 PGA/PLA, 95/5 PLA/PGA, and
polydioxanone (PDO) nonwoven mats, and perforated thin sheets of
60/40 PLA/PCL (polycaprolactone) or 65/35 PGA/PCL.
A variety of biocompatible polymers can be used to make fibers for
the synthetic portion. Examples of suitable biocompatible,
bioabsorbable polymers that could be used include polymers selected
from the group consisting of aliphatic polyesters, poly(amino
acids), copoly(ether-esters), polyalkylenes oxalates, polyamides,
poly(iminocarbonates), polyorthoesters, polyoxaesters,
polyamidoesters, polyoxaesters containing amine groups,
poly(anhydrides), polyphosphazenes, biomolecules and blends
thereof. For the purpose of this disclosure aliphatic polyesters
include but are not limited to homopolymers and copolymers of
lactide (which includes lactic acid, D-,L- and meso lactide),
glycolide (including glycolic acid), .epsilon.-caprolactone,
p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate
(1,3-dioxan-2-one), alkyl derivatives of trimethylene carbonate,
.delta.-valerolactone, .beta.-butyrolactone, .gamma.-butyrolactone,
.epsilon.-decalactone, hydroxybutyrate (repeating units),
hydroxyvalerate (repeating units), 1,4-dioxepan-2-one (including
its dimer 1,5,8,12-tetraoxacyclotetradecane-7,14-dione),
1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one
2,5-diketomorpholine, pivalolactone,
.alpha.,.alpha.-diethylpropiolactone, ethylene carbonate, ethylene
oxalate, 3-methyl-1,4-dioxane-2,5-dione,
3,3-diethyl-1,4-dioxan-2,5-dione, 6,8-dioxabicycloctane-7-one,
copolymers, and polymer blends thereof. Other synthetic polymers
are known in the art and may be used within the scope of this
disclosure.
The particular polymer may be selected depending on one or more of
the following factors: (a) bio-absorption (or bio-degradation)
kinetics; (b) in-vivo mechanical performance; and (c) cell response
to the material in terms of cell attachment, proliferation,
migration and differentiation and (d) biocompatibility. With
respect to the bio-absorption kinetics, it is known to control
resorption rates by selection of the polymer or copolymer. By way
of example, it is known that a 35:65 blend of
.epsilon.-caprolactone and glycolide is a relatively fast absorbing
polymer and a 40:60 blend of .epsilon.-caprolactone and (L)lactide
is a relatively slow absorbing polymer. Optionally, two or more
polymers or copolymers could then be blended together to form a
foam having several different physical properties.
In some orthopaedic applications, it is desirable to combine the
tissue remodeling properties of ECM with the controlled resorption
properties of synthetic foams, mats, or sheets. Thus, methods are
provided for making porous scaffolds for the repair or regeneration
of a body tissue, wherein the scaffolds comprise an ECM component
and a synthetic portion. According to one illustrative embodiment,
there is provided a method of making an implantable scaffold for
repairing damaged or diseased tissue. The method includes the steps
of suspending pieces of an ECM material in a liquid and mixing a
polymer solution into the liquid. The mixture is formed into a mass
and, subsequently, the liquid is driven off so as to form
interstices in the mass. In another embodiment, the method includes
suspending pieces of an ECM material in a liquid and forming a
mass. A polymer mat, for example, a mesh or nonwoven, is coated
with the ECM material, and, subsequently, the liquid is driven off,
forming a foam having a combination of mechanical and biological
features.
In one specific implementation of an exemplary embodiment, the
liquid is driven off by lyophilizing the ECM and synthetic material
and the liquid in which they are suspended. In such a manner, the
liquid is sublimed thereby forming the interstices in the mass.
The material density and pore size of the scaffold may be varied by
controlling the rate of freezing of the suspension. The amount of
water into which the pieces of extracellular matrix material are
suspended may also be varied to control the material density and
pore size of the resultant scaffold. Furthermore, as discussed
above, the resorption rate may be controlled by varying the
synthetic polymer structure or composition.
In accordance with another exemplary embodiment, there is provided
an implantable scaffold for repairing or regenerating tissue
prepared by the process described above.
Thus, one aspect of this disclosure is directed to a method of
making an implantable scaffold for repairing or regenerating body
tissue, the method comprising the steps of suspending ECM material
in a liquid to form a slurry, adding a synthetic portion to the
slurry to make an ECM/synthetic composition, freezing the
composition to form crystals therein, and driving off the crystals
to form a foam. In one illustrated embodiment, the ECM is
comminuted. In another illustrated embodiment, the liquid is water,
the crystals are ice, and the crystals are driven off by
lyophilization.
In another aspect of this disclosure an implantable scaffold for
repairing or regenerating body tissue is provided, the scaffold
comprising a porous ECM foam and a synthetic mat imbedded
therein.
Yet another aspect is an implantable scaffold comprising a mass of
ECM intermixed with a fibrous synthetic portion in a composition
dried to have a desired porosity.
Still, another aspect of this invention is an implantable scaffold
comprising a porous foam comprising ECM and a synthetic portion
distributed within the foam.
The above and other features of the present disclosure will become
apparent from the following description and the attached
drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
The detailed description particularly refers to the accompanying
figures in which:
FIG. 1 is a scanning electron micrograph showing the surface of a
porous three-dimensional SIS/synthetic polymer hybrid scaffold
comprising a nonwoven, needled VICRYL.RTM. sheet (Ethicon, Inc,
Somerville, N.J.) coated with SIS foam. Wet SIS slurry was coated
on the VICRYL.RTM. sheet, and the assembly was needled and then
lyophilized;
FIG. 2 is a scanning electron micrograph showing the surface of a
porous three-dimensional SIS/synthetic polymer hybrid scaffold in
which the SIS portion is sandwiched between two nonwoven
VICRYL.RTM. The assembly was needled and then lyophilized.
FIG. 3 is a scanning electron micrograph showing the surface of a
porous three-dimensional SIS/synthetic polymer hybrid scaffold
comprising a nonwoven, non-needled VICRYL.RTM. sheet coated with
SIS foam. Wet SIS slurry was coated on the VICRYL.RTM. sheet. The
construct was centrifuged, additional SIS slurry was added,
followed by additional centrifugation. The construct was needled
and then lyophilized.
DETAILED DESCRIPTION OF THE DISCLOSURE
The present disclosure relates to porous scaffolds for implanting
into the body of a patient to repair or regenerate damaged or
diseased tissue. The porous scaffold is constructed from a
naturally occurring extracellular material and a synthetic polymer.
For example, the scaffold may be constructed from a mat of mesh or
nonwoven synthetic material coated with SIS, a mixture of SIS and a
synthetic polymer, or from layers of SIS and synthetic polymer. The
material density, pore size, and resorption rate of the porous
scaffold may be varied to fit the needs of a given scaffold
design.
Such porous scaffolds may be fabricated by first suspending pieces
of an ECM material in a liquid. As used herein, the term
"suspending" is intended to include any placement of a solid (e.g.,
pieces of ECM) in a liquid whether or not an actual suspension is
created. As such, the term "suspending" is intended to include any
mixing of a solid in a liquid or any other placement of a solid in
a liquid. As a result, the term "suspension" is likewise not
intended to be limited to suspensions, but rather is intended to
mean any mass having a solid present in a liquid. Suspension of the
pieces of ECM material in the liquid forms a mass in the form of,
for example, a "slurry". The slurry may be used to coat a mat of
mesh or nonwoven synthetic portion or a solution of a synthetic
polymer may be added to the slurry, and the liquid may then be
subsequently driven off of so as to form interstices therein. The
liquid may be driven off in a number of different manners. For
example, as will herein be described in greater detail, the liquid
may be driven off via sublimation in a freeze drying process.
Alternatively, the liquid may also be driven off by subjecting the
suspension to vacuum under a controlled heating process. The liquid
may also be driven off from the suspension ultrasonically.
Microwave energy may also be utilized to drive the liquid off of
the suspension. Moreover, the liquid may include a water-soluble
filler that is driven off, for example, by use of an alcohol.
While any of the aforementioned processes for driving off the
liquid from the suspension may be used, along with any other
process known by one skilled in the art, the processes of the
present disclosure will herein be exemplary described in regard to
a lyophilization process (i.e., freeze drying). However, it should
be understood that such a description is merely exemplary in nature
and that any one or more of the aforedescribed processes for
driving off the liquid from the suspension may be utilized to fit
the needs of a given scaffold design or process design.
As discussed above, one useful process for fabricating the porous
scaffolds of the present disclosure is by lyophilization. In this
case, an ECM/polymer composition is frozen and subsequently
lyophilized. Freezing the suspension causes the liquid to
crystallize. These crystals are then sublimed during the
lyophilization process, thereby leaving interstices in the material
in the spaces previously occupied by the crystals. The material
density and pore size of the resultant scaffold may be varied by
controlling, among other things, the rate of freezing of the
suspension and/or the amount of water in which the ECM material is
suspended in at the start of the freezing process.
As a specific example of this process, fabrication of porous
SIS/synthetic hybrid scaffolds by lyophilization will be described
in detail. However, it should be appreciated that although the
example is herein described in regard to an SIS/synthetic scaffold,
fabrication of a scaffold constructed from other ECM materials and
synthetic polymers may also be performed in a similar manner.
The first step in fabricating a porous scaffold with a desired pore
size and density is the procurement of comminuted SIS.
Illustratively, scissor-cut SIS runners (.about.6'' long) are
positioned in a 1700 series COMITROL.RTM. machine, commercially
available from Urschel Laboratories (Valpraiso, Ind.). The SIS
material is processed and thereafter collected in a receptacle at
the output of the machine. The material is then processed through
the machine a second time under similar conditions. The resultant
material is a "slurry" of SIS material (thin, long SIS fibers
.about.200 microns thick.times.1-5 mm long) suspended in a
substantially uniform manner in water. Although the suspension is
herein described as being formed as a byproduct of the comminuting
process, it should be appreciated that the pieces of SIS may be
suspended in the liquid (i.e., water) in other manners known to
those skilled in the art. Furthermore, while other methods are
known for comminuting SIS, it is understood that for the purposes
of the present disclosure, comminuted SIS comprises ribbon-like or
string-like fibers wherein at least some of the individual pieces
of ECM and SIS material have lengths greater than their widths and
thicknesses. Such fibers may be interlaced to provide a felt-like
material, if desired.
Process parameters can be varied using the above-identified 1700
series COMITROL.RTM. machine, including the choice of blade used,
whether water is used, the amount of water used, the speed at which
the blades turn, and the number of times the material is passed
through the machine. As an example, cutting head 140084-10 and a
VERICUT.RTM., sealed impeller from Urschel Laboratories may be
used, with a flow of water of about two (2) gallons per minute,
with the blade running at a constant speed of about 9300 rpm. A
first pass through the machine at these parameters will produce
fibrous SIS material of varying sizes, and a second pass will
produce SIS fibers of a more uniform size. By way of example, the
comminuted material may be tested to determine if it has the
consistency of that which is desired for use in regard to the
illustrative embodiments described herein by the following process:
the comminuted SIS suspension or slurry is centrifuged, excess
water is poured off and the remaining slurry is poured into a dish.
By hand, a small amount of the comminuted SIS material in the dish
is pinched between the thumb and index finger and gently lifted
from the dish. Illustratively, at least a small amount of
additional SIS, beyond the portion pinched between the thumb and
index finger, will lift along with the material that has been
pinched. This additional comminuted SIS material lifts with the
material that is between the thumb and index finger because the
individual pieces of comminuted SIS material are comingled or
intertwined. Prior art methods of "comminuting" SIS using a freezer
mill produce particles, rather then ribbon-like fibers. The prior
art particles are not capable of significant intertwining and, for
purposes of the present disclosure, are not included within the
definition of comminuted SIS. See copending U.S. patent application
Ser. No. 10/195,354 entitled "Porous Extracellular Matrix Scaffold
and Method".
The terms "cohesive ECM", "cohesive SIS", "cohesive ECM pieces" and
"cohesive SIS pieces" are used herein to respectively denote ECM or
SIS material that has been comminuted or otherwise physically
processed to produce ECM or SIS pieces that are capable of
comingling or intertwining (in the wet or dry state) to form a mass
of discrete pieces of ECM or SIS that remain massed together under
some conditions (such as under gravity), regardless of the shape or
shapes of the individual ECM or SIS pieces. One method of
demonstrating that the ECM or SIS material comprises cohesive
pieces is the "pinch test" described in the preceding paragraph.
Examination of the final ECM or SIS product produced may also
provide evidence that the base material comprised cohesive ECM or
SIS pieces. Illustratively, the ECM or SIS pieces are sufficiently
cohesive to each other (or to other pieces in the mix or slurry)
that they remain unified throughout the process used to produce the
foam structure.
A polymer solution is also prepared, as is known in the art. By way
of example, a 95:5 weight ratio solution of 60/40 PLA/PCL is made
and poured into a flask. The flask is placed in a water bath,
stirring at 60-70.degree. C. for 5 hrs. The solution is filtered
using an extraction thimble, extra coarse porosity, type ASTM
170-220 (EC) and stored in flasks.
Thereafter, the comminuted SIS suspension is mixed or layered with
the polymer solution. In another embodiment, the SIS suspension is
used with or without an intermixed polymer solution to coat a mat
of mesh or nonwoven polymer. The SIS/polymer composition is frozen
and lyophilized (i.e., freeze dried). In particular, the
SIS/polymer composition is frozen at a controlled rate of
temperature drop to control the size of the formed crystals. Once
frozen, and without allowing the material to thaw, the
lyophilization process sublimes the crystals directly to a vapor
under vacuum and low temperatures. This leaves voids or interstices
in the spaces previously occupied by the crystals. In the
embodiments wherein the polymer component is a mat of mesh or
nonwoven material, the SIS forms a foam around the polymer
component, and, depending on the size of the interstices, the foam
may form therethrough.
Any method for freezing the composition to a desired temperature
may be used Likewise, any commercially available lyophilizer may be
used for the lyophilization process. One exemplary machine for
performing the lyophilization process is a Virtis GENESIS.TM.
Series lyophilizer that is commercially available from SP
Industries, Inc. (Gardiner, N.Y.).
The process parameters of the aforedescribed fabrication process
may be varied to produce scaffolds of varying pore sizes and
material densities. For example, the rate at which the suspension
is frozen, the amount of water present in the suspension, and the
compactness of the ECM material each may be varied to produce
scaffolds of varying pore sizes and material densities.
For instance, to produce scaffolds having a relatively large pore
size and a relatively low material density, the composition may be
frozen at a slow, controlled rate (e.g., -1.degree. C./min or less)
to a temperature of about -20.degree. C., followed by
lyophilization of the resultant mass. To produce scaffolds having a
relatively small pore size and a relatively high material density,
the SIS suspension may be tightly compacted by centrifuging the
material to remove a portion of the liquid (e.g., water) in a
substantially uniform manner prior to mixing with the polymer
component. If desired, the fibers of the hybrid foams may be
crosslinked, for example physically, chemically, or enzymatically,
to increase mechanical strength of the scaffold.
Additionally, because of the porosity of the scaffolds, the
scaffolds of the present disclosure may be used to deliver various
biologically active agents to a damaged tissue, in addition to
those already present in the ECM, including one or more exogenous
biologically-derived agents or substances, one or more cell types,
one or more biological lubricants, one or more biocompatible
inorganic materials, one or more biocompatible synthetic polymers
and one or more biopolymers. Various biologically active agents can
be added to the foams, for example, prior to lyophilization, or
subsequent to lyophilization by adsorption onto the surface or back
filling into the foams after the foams are made. For example, the
pores of the foam may be partially or completely filled with
biocompatible resorbable synthetic polymers or biopolymers (such as
collagen or elastin) or biocompatible inorganic materials (such as
hydroxyapatite) and combinations thereof.
"Bioactive agents" include one or more of the following:
chemotactic agents; therapeutic agents (e.g. antibiotics, steroidal
and non-steroidal analgesics and anti-inflammatories,
anti-rejection agents such as immunosuppressants and anti-cancer
drugs); various proteins (e.g. short chain peptides, bone
morphogenic proteins, glycoprotein and lipoprotein); cell
attachment mediators; biologically active ligands; integrin binding
sequence; ligands; various growth and/or differentiation agents
(e.g. epidermal growth factor, IGF-I, IGF-II, TGF-.beta. I-III,
growth and differentiation factors, vascular endothelial growth
factors, fibroblast growth factors, platelet derived growth
factors, insulin derived growth factor and transforming growth
factors, parathyroid hormone, parathyroid hormone related peptide,
bFGF; TGF.sub..beta. superfamily factors; BMP-2; BMP-4; BMP-6;
BMP-12; sonic hedgehog; GDF5; GDF6; GDF8; PDGF); small molecules
that affect the upregulation of specific growth factors;
tenascin-C; hyaluronic acid; chondroitin sulfate; fibronectin;
decorin; thromboelastin; thrombin-derived peptides; heparin-binding
domains; heparin; heparan sulfate; DNA fragments and DNA plasmids.
If other such substances have therapeutic value in the orthopaedic
field, it is anticipated that at least some of these substances
will have use in the present invention, and such substances should
be included in the meaning of "bioactive agent" and "bioactive
agents" unless expressly limited otherwise.
"Biologically derived agents" include one or more of the following:
bone (autograft, allograft, and xenograft) and derivates of bone;
cartilage (autograft, allograft, and xenograft), including, for
example, meniscal tissue, and derivatives; ligament (autograft,
allograft, and xenograft) and derivatives; derivatives of
intestinal tissue (autograft, allograft, and xenograft), including
for example submucosa; derivatives of stomach tissue (autograft,
allograft, and xenograft), including for example submucosa;
derivatives of bladder tissue (autograft, allograft, and
xenograft), including for example submucosa; derivatives of
alimentary tissue (autograft, allograft, and xenograft), including
for example submucosa; derivatives of respiratory tissue
(autograft, allograft, and xenograft), including for example
submucosa; derivatives of genital tissue (autograft, allograft, and
xenograft), including for example submucosa; derivatives of liver
tissue (autograft, allograft, and xenograft), including for example
liver basement membrane; derivatives of skin tissue; platelet rich
plasma (PRP), platelet poor plasma, bone marrow aspirate,
demineralized bone matrix, insulin derived growth factor, whole
blood, fibrin and blood clot. Purified ECM and other collagen
sources are also intended to be included within "biologically
derived agents." If other such substances have therapeutic value in
the orthopaedic field, it is anticipated that at least some of
these substances will have use in the present invention, and such
substances should be included in the meaning of "biologically
derived agent" and "biologically derived agents" unless expressly
limited otherwise.
"Biologically derived agents" also include bioremodelable
collageneous tissue matrices. The expressions "bioremodelable
collagenous tissue matrix" and "naturally occurring bioremodelable
collageneous tissue matrix" include matrices derived from native
tissue selected from the group consisting of skin, artery, vein,
pericardium, heart valve, dura mater, ligament, bone, cartilage,
bladder, liver, stomach, fascia and intestine, tendon, whatever the
source. Although "naturally occurring bioremodelable collageneous
tissue matrix" is intended to refer to matrix material that has
been cleaned, processed, sterilized, and optionally crosslinked, it
is not within the definition of a naturally occurring
bioremodelable collageneous tissue matrix to purify the natural
fibers and reform a matrix material from purified natural fibers.
The term "bioremodelable collageneous tissue matrices" includes
"extracellular matrices" within its definition.
"Cells" include one or more of the following: chondrocytes;
fibrochondrocytes; osteocytes; osteoblasts; osteoclasts;
synoviocytes; bone marrow cells; mesenchymal cells; stromal cells;
stem cells; embryonic stem cells; precursor cells derived from
adipose tissue; peripheral blood progenitor cells; stem cells
isolated from adult tissue; genetically transformed cells; a
combination of chondrocytes and other cells; a combination of
osteocytes and other cells; a combination of synoviocytes and other
cells; a combination of bone marrow cells and other cells; a
combination of mesenchymal cells and other cells; a combination of
stromal cells and other cells; a combination of stem cells and
other cells; a combination of embryonic stem cells and other cells;
a combination of precursor cells isolated from adult tissue and
other cells; a combination of peripheral blood progenitor cells and
other cells; a combination of stem cells isolated from adult tissue
and other cells; and a combination of genetically transformed cells
and other cells. If other cells are found to have therapeutic value
in the orthopaedic field, it is anticipated that at least some of
these cells will have use in the present invention, and such cells
should be included within the meaning of "cell" and "cells" unless
expressly limited otherwise. Illustratively, in one example of
embodiments that are to be seeded with living cells such as
chondrocytes, a sterilized implant may be subsequently seeded with
living cells and packaged in an appropriate medium for the cell
type used. For example, a cell culture medium comprising Dulbecco's
Modified Eagles Medium (DMEM) can be used with standard additives
such as non-essential amino acids, glucose, ascorbic acid, sodium
pyrovate, fungicides, antibiotics, etc., in concentrations deemed
appropriate for cell type, shipping conditions, etc.
"Biological lubricants" include: hyaluronic acid and its salts,
such as sodium hyaluronate; glycosaminoglycans such as dermatan
sulfate, heparan sulfate, chondroiton sulfate and keratan sulfate;
synovial fluid and components of synovial fluid, including mucinous
glycoproteins (e.g. lubricin), tribonectins, articular cartilage
superficial zone proteins, surface-active phospholipids,
lubricating glycoproteins I, II; vitronectin; and rooster comb
hyaluronate. "Biological lubricant" is also intended to include
commercial products such as ARTHREASE.TM. high molecular weight
sodium hyaluronate, available in Europe from DePuy International,
Ltd. of Leeds, England, and manufactured by Bio-Technology General
(Israel) Ltd., of Rehovot, Israel; SYNVISC.RTM. Hylan G-F 20,
manufactured by Biomatrix, Inc., of Ridgefield, N.J. and
distributed by Wyeth-Ayerst Pharmaceuticals of Philadelphia, Pa.;
HYLAGAN.RTM. sodium hyaluronate, available from Sanofi-Synthelabo,
Inc., of New York, N.Y., manufactured by FIDIA S.p.A., of Padua,
Italy; and HEALON.RTM. sodium hyaluronate, available from Pharmacia
Corporation of Peapack, N.J. in concentrations of 1%, 1.4% and 2.3%
(for ophthalmologic uses). If other such substances have
therapeutic value in the orthopaedic field, it is anticipated that
at least some of these substances will have use in the present
invention, and such substances should be included in the meaning of
"biological lubricant" and "biological lubricants" unless expressly
limited otherwise.
"Biocompatible polymers" is intended to include both synthetic
polymers and biopolymers (e.g. collagen). Examples of biocompatible
polymers include: polyesters of [alpha]-hydroxycarboxylic acids,
such as poly(L-lactide) (PLLA) and polyglycolide (PGA);
poly-p-dioxanone (PDO); polycaprolactone (PCL); polyvinyl alcohol
(PVA); polyethylene oxide (PEO); polymers disclosed in U.S. Pat.
Nos. 6,333,029 and 6,355,699; and any other bioresorbable and
biocompatible polymer, co-polymer or mixture of polymers or
co-polymers that are utilized in the construction of prosthetic
implants. In addition, as new biocompatible, bioresorbable
materials are developed, it is expected that at least some of them
will be useful materials from which orthopaedic devices may be
made. It should be understood that the above materials are
identified by way of example only, and the present invention is not
limited to any particular material unless expressly called for in
the claims.
"Biocompatible inorganic materials" include materials such as
hydroxyapatite, all calcium phosphates, alpha-tricalcium phosphate,
beta-tricalcium phosphate, calcium carbonate, barium carbonate,
calcium sulfate, barium sulfate, polymorphs of calcium phosphate,
sintered and non-sintered ceramic particles, and combinations of
such materials. If other such substances have therapeutic value in
the orthopaedic field, it is anticipated that at least some of
these substances will have use in the present invention, and such
substances should be included in the meaning of "biocompatible
inorganic material" and "biocompatible inorganic materials" unless
expressly limited otherwise.
It is expected that various combinations of bioactive agents,
biologically derived agents, cells, biological lubricants,
biocompatible inorganic materials, biocompatible polymers can be
used with the devices of the present invention.
EXAMPLE 1
An aqueous suspension of SIS ("slurry") is made, of approximately 8
mg dry weight of comminuted SIS material per mL of water. The
slurry is placed within a beaker on a stirring plate for
approximately 3 minutes to ensure that the SIS is evenly dispersed
in the suspension.
A polymer solution of 95:5 weight ratio solution of 60/40 PLA/PCL
is made and poured into a flask. The flask is placed in a water
bath, stirring at 60-70EC for 5 hrs. The solution is filtered using
an extraction thimble, extra coarse porosity, type ASTM 170-220
(EC) and stored in flasks.
An equal amount of the polymer solution is added to the SIS slurry,
to form an SIS/polymer mixture. The mixture is stirred on a
stirring plate to make sure that the SIS and polymer are evenly
dispersed in the suspension.
The porous scaffolds are obtained by freezing a comminuted SIS
suspension at a slow, controlled rate (-1.degree. C./min or less)
to -20.degree. C., followed by lyophilization, as follows: a
slow-freeze ethanol bath is prepared by pouring enough ethanol to
obtain about a 1 centimeter head in a flat-bottomed plastic
container large enough to hold four 24-well culture plates. The
container is placed in a -20.degree. C. freezer. Under a sterile
hood using sterile conditions, an approximately 3 ml aliquot of the
comminuted SIS/polymer material is placed in each well of the
tissue culture plates. The culture plates are then placed into the
ethanol freeze bath and allowed to freeze overnight.
The frozen plates are then removed from the ethanol bath and placed
in a suitable lyophilizer, such as the Virtis GENESIS.TM. Series
lyophilizer described above. The parameters used in the
lyophilization process include a first period at a primary drying
temperature of 13.degree. C. for 8 hours, followed by a second
period at a secondary drying temperature of 35.degree. C. for 4
hours.
The resulting foam may be shaped or sculpted for the particular
application. It is also understood that the mold could be provided
in the desired shape, reducing or obviating the need for sculpting
or trimming.
While Example 1 is directed to porous SIS/polymer scaffolds having
a relatively large pore size, it is understood that the freezing
and lyophilization profiles may be adjusted to produce scaffolds of
desired size. Copending U.S. application Ser. No. 10/195,354
entitled "Porous Extracellular Matrix Scaffold and Method", already
incorporated by reference, provides various freezing and
lyophilization profiles for the control of porosity.
EXAMPLE 2
An SIS slurry and a polymer solution are prepared as in Example 1.
However, rather than mixing a solution of polymer with the SIS, the
solution of the polymer is layered over the mass. The layered
mixture is then frozen and lyophilized as in Example 1, forming a
foam having several layers of different mechanical and biological
composition. However, because the foam layers are formed together
and expand somewhat into the interstices of the adjacent layer,
there would not be a discrete demarcation between the synthetic
foam and the ECM foam. Allowing the layers to mix slightly prior to
lyophilization will increase the width of the transition zone
between the layers.
EXAMPLE 3
In this example, a layered construct is formed wherein the scaffold
has an SIS foam component and a synthetic mat component.
An SIS slurry is prepared as in Example 1. Next, a 2 cm.times.2 cm
piece of a 90/10 PGA/PLA mat is presoaked in water and then placed
in the beaker with the SIS slurry. The 90/10 PGA/PLA piece is fully
immersed within the slurry, resulting in an SIS-coated mat, having
a thick coating of the SIS material on the synthetic mat. Several
such SIS-coated 90/10 PGA/PLA mats are prepared. The coated mats
are immediately transferred to a -80.degree. C. freezer. After
freezing, the coated mats are lyophilized as in Example 1.
While 90/10 PGA/PLA is used for the mat in this example, it is
understood that the additional structural component can be made of
any biocompatible material, including bioabsorbable materials such
as polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone
(PCL), polydioxanone (PDO), trimethylene carbonate (TMC), polyvinyl
alcohol (PVA), copolymers or blends thereof. Furthermore, it is
understood that additional structure may be provided by a variety
of woven and nonwoven felts, meshes, textiles or other materials.
As with the synthetic foam component, the composition of the
additional structural component may be selected to provide an
appropriate resorption rate.
EXAMPLE 4
An SIS-coated 90/10 PGA/PLA mat is prepared as in Example 3. The
SIS-coated 90/10 PGA/PLA mat is "needled" using stainless steel
needle pad (having a plastic base with several closely spaced,
about 1 mm apart, stainless steel needles). The needling procedure
involved applying the wet hybrid implant to the needle pad and
applying thumb pressure to drive the needles through the thickness
of the implant. The needling is believed to enhance mechanical
entangling between the synthetic and SIS portions of the hybrid
scaffold, resulting in between adherence of the layers. The implant
is then transferred to the -80.degree. C. freezer, and subsequently
lyophilized, as in Example 3. FIG. 1 shows a similar foam made with
a VICRYL.RTM. mat. FIG. 2 is also similar, having several layers of
VICRYL.RTM..
EXAMPLE 5
An SIS slurry is prepared as in Example 1. 2 cm diameter 90/10
PGA/PLA mats are placed into individual wells of a six well tissue
culture plate. 4 mL of the SIS slurry is pipetted onto each 90/10
PGA/PLA mat. The plate is centrifuged at 2000 rpm for 2 minutes.
The water is decanted off and another 2 mL of the slurry is added
and the plates are centrifuged in the same way. This treatment
resulted in an approximately 1 mm thick coating of SIS on the 90/10
PGA/PLA disk. Some of these implants are needled in the same way as
described in Example 4. Others were not needled at all. The
implants are then frozen and lyophilized as described in Example 3.
FIG. 3 shows a similar foam using VICRYL.RTM..
As can be seen from the forgoing description, the concepts of the
present disclosure provide numerous advantages. For example, the
concepts of the present disclosure provide for the fabrication of a
porous implantable scaffold which may have varying mechanical
properties to fit the needs of a given scaffold design. For
instance, the pore size and the material density may be varied to
produce a scaffold having a desired mechanical configuration. In
particular, such variation of the pore size and the material
density of the scaffold is particularly useful when designing a
scaffold which provides for a desired amount of cellular migration
therethrough, while also providing a desired amount of structural
rigidity. Additionally, by selecting an appropriate polymer,
mechanical strength and resorption rates can be controlled, to
provide mechanical support for a desired length of time subsequent
to implantation.
While the disclosure is susceptible to various modifications and
alternative forms, specific exemplary embodiments thereof have been
shown by way of example in the drawings and has herein be described
in detail. It should be understood, however, that there is no
intent to limit the disclosure to the particular forms disclosed,
but on the contrary, the intention is to cover all modifications,
equivalents, and alternatives falling within the spirit and scope
of the disclosure.
There are a plurality of advantages of the present disclosure
arising from the various features of the apparatus and methods
described herein. It will be noted that alternative embodiments of
the apparatus and methods of the present disclosure may not include
all of the features described yet still benefit from at least some
of the advantages of such features. Those of ordinary skill in the
art may readily devise their own implementations of an apparatus
and method that incorporate one or more of the features of the
present disclosure and fall within the spirit and scope of the
present disclosure.
* * * * *
References